2. Academic Validation
  3. Adipose Triglyceride Lipase-Mediated Adipocyte Lipolysis Exacerbates Acute Pancreatitis Severity in Mouse Models and Patients

Adipose Triglyceride Lipase-Mediated Adipocyte Lipolysis Exacerbates Acute Pancreatitis Severity in Mouse Models and Patients

  • Am J Pathol. 2024 May 3:S0002-9440(24)00165-2. doi: 10.1016/j.ajpath.2024.03.014.
Xiaochun Xie 1,  Yang Liu 1,  Qi Yang 2,  Xiaojie Ma 2,  Yingying Lu 1,  Yuepeng Hu 2,  Guofu Zhang 2,  Lu Ke 2,  Zhihui Tong 2,  Yuxiu Liu 3,  Jing Xue 4,  Guotao Lu 5,  Weiqin Li 6
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Nanjing Jinling Hospital, Medical School of Southeast University, Nanjing, China; Medical School of Southeast University, Nanjing, China.
  • 2 Department of Critical Care Medicine, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 3 Department of Critical Care Medicine, Nanjing Jinling Hospital, Nanjing Medical University, Nanjing, China.
  • 4 State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Centre, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 5 Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. Electronic address: gtlu@yzu.edu.cn.
  • 6 Department of Critical Care Medicine, Nanjing Jinling Hospital, Medical School of Southeast University, Nanjing, China; Medical School of Southeast University, Nanjing, China; Department of Critical Care Medicine, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: liweiqindr@nju.edu.cn.
PMID: 38705384 DOI: 10.1016/j.ajpath.2024.03.014
Abstract

Dyslipolysis of adipocytes has played a critical role in various diseases. Adipose triglyceride Lipase (ATGL) is a rate-limiting Enzyme in adipocyte autonomous lipolysis. However, whether the degree of adipocyte lipolysis relates to the prognoses in acute pancreatitis (AP) and the role of ATGL-mediated lipolysis in the pathogenesis of AP remain elusive. The visceral adipose tissue consumption rate in the acute stage was measured in both patients with AP and mouse models. Lipolysis levels and ATGL expression were detected in caerulein-induced AP models. CL316,243, a lipolysis stimulator, and adipose tissue-specific ATGL knockout mice were used to further investigate the role of lipolysis in AP. The ATGL-specific inhibitor, atglistatin, was used in C57Bl/6N and ob/ob AP models. This study found that increased visceral adipose tissue consumption rate in the acute phase was independently associated with adverse prognoses in patients with AP, which was validated in mice AP models. Lipolysis of adipocytes was elevated in AP mice. Stimulation of lipolysis could aggravate AP. Genetic blockage of ATGL specifically in adipocytes was able to alleviate the damage to AP. The application of atglistatin could effectively protect against AP in both lean and obese mice. These findings demonstrated that ATGL-mediated adipocyte lipolysis exacerbates AP and highlighted the therapeutic potential of ATGL as a drug target for AP.

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